M-Clorophenylpiperazine (m-CPP), a direct serotonin receptor agonist, has been studied extensively this year by our group in rodents, monkeys and, for the first time, in humans. In normal volunteers, m-CPP's neuroendocrine effects on prolactin and cortisol exhibited a clear dose-dependent relationship. These changes were blocked by the serotonin receptor antagonist, metergoline. M-clorophenylpiperazine also elicited changes in temperature, behavior and adrenocorticotropin release. Studies using m-CPP as a probe of serotonin CNS function in different psychiatric patient groups and during psychoactive drug treatment conditions are underway. Marked effects of antidepressant drugs, especially MAO-inhibitors, have been observed on plasma and cerebrospinal fluid melatonin and serotonin concentrations in monkeys and humans. The localization of a number of neuropeptides, including atrial natriuretic peptide, enkephalins, metorphamide and melanin concentrating hormone has been delineated in rodent brain. Antibodies to Beta-endorphin have been identified and characterized in human plasma.